Major objective of the proposed studies is better understanding of the role in gastrointestinal pathophysiology of IgA, the principal immunoglobulin in gut tissues and fluids. Studies to be conducted include (1) ultrastructural localization of IgA and its secretory component in human intestinal epithelium, and (2) evaluation of the postulated role of intestinal IgA as a barrier to penetration of the gut epithelium by bacteria and macromolecules. The ultrastructural locations of IgA and secretory component are to be determined by peroxidase-labeled antibody techniques. The barrier function of IgA is to be evaluated by in vivo studies in the rat and rabbit of the effect of IgA on adherence of bacteria to gut epithelium, and mechanisms by which oral immunization affects intestinal uptake of macromolecules. Rationale of the studies is as follows: Distrubed immunological behavior of the gut may be important in the pathogenesis of serious bowel diseases, particularly neoplasms, regional enteritis and chronic ulcerative colitis. Many aspects of normal and abnormal immunological behavior of the bowel have not been adequately investigated, however. A better understanding of gastrointestinal immunoglobulins, particularly IgA, could contribute significantly to understanding immunological defense mechanism of the gut and disorders in which immunological reactions may be pathogenetically involved.